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BCR-ABL oncogene, the molecular hallmark of chronic myelogenous leukemia,
arises in a primitive hematopoietic stem cell that has the capacity for both
differentiation and self-renewal. Its product, Bcr-Abl protein, has been shown
to activate signal transducers and activators of transcription 3 (STAT3) and to
promote self-renewal in embryonic stem (ES) cells, even in the absence of
leukemia inhibitory factor (LIF). MEK kinase 1 (MEKK1) is a 196-kDa
mitogen-activated protein kinase (MAPK) kinase kinase involved in Bcr-Abl signal
transduction. To investigate the role of MEKK1 in Bcr-Abl-induced transformation
of stem cells, p210 Bcr-Abl was stably transfected into wild-type (WT(p210)) and
MEKK1-/- (MEKK1-/-(p210)) ES cells.
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